| 1. |
- Isaksson, Johan, et al.
(författare)
-
Predictors of long-term survival and recurrence patterns after definitive chemoradiotherapy in stage III NSCLC – a multicenter cohort study from Mid Sweden
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: Stage III NSCLC is heterogeneous but often recurs despite intensive treatment with curative intent. Clinical tools to predict the risk and pattern of recurrence and long-term survival in individual patients are largely lacking. Methods: NSCLC stage III patients (N=193) treated 2009-2018 with definitive, curatively intended chemoradiotherapy (CRT, 60Gy+) were retrospectively identified from three healthcare regions in Mid Sweden. Outcome variables included overall survival (OS), progression-free survival (PFS) and recurrence patterns. Results: Median follow-up of patients alive was 52 months. 1, 2 and 5-year OS was 80%, 63% and 34% with a mOS of 32 months. Pre-treatment serum inflammatory markers were associated with inferior OS, including leukocyte count > 10 (HR 1.58, 95% CI 1.08-2.31, p=0.018) and CRP > 5 (HR 1.81, 95% CI 1.16-2.83, p=0.009). CRP remained independently associated with OS in multivariable analysis, HR 1.67 (1.05-2.65, p=0.029). No other pre-treatment variable was significantly associated with OS. Progressive disease (PD) was documented in 65% of patients after a median time of 9.5 months, 96% within 3 years from CRT, and was typically either distant or locoregional (12% mixed). Distant PD developed earlier (6.3 months) than locoregional PD (11.5 months; p=0.052). N3 disease (OR 2.7, 95% CI 1.2-6.3,; p=0.022) and presence of driver mutations (OR 4.6, 95% CI 1.5-14.0; p=0.0076) increased the risk of distant PD, while ≥2 concurrent chemotherapy courses was protective of locoregional PD (OR 0.38, 9% CI 0.1-1.0; p=0.049). Brain metastases were the first indication of PD in 22 patients (12%) and were in all cases isolated without synchronous extracranial PD. A post-CRT 18F-FDG-PET SUVmax of ≥7 was associated with a shorter time to PD (HR 0.41, 95% CI 0.21-0.79, p=0.008). Conclusions: The study reinforces the prognostic role of systemic inflammation in stage III NSCLC and provides clinically useful indicators of relapse pattern as a basis for rational disease monitoring following CRT.
|
|
| 2. |
- Abele, Dace, et al.
(författare)
-
Including the liver in the visceral allograft: Impact on donor-specific anti-HLA antibodies and long-term outcomes
- 2024
-
Ingår i: HUMAN IMMUNOLOGY. - 0198-8859 .- 1879-1166. ; 85:2
-
Tidskriftsartikel (refereegranskat)abstract
- Humoral immunity emerges as a risk factor for graft failure after visceral transplantation (VTx) and development of donor-specific anti-HLA antibodies (DSAs) has been linked with poor outcomes. In most cases, a simultaneous liver transplant can be safely performed in sensitized patients with DSA and appears protective against lymphocytotoxic antibodies. We investigated the incidence of acute (AR) and chronic rejection (CR) in 32 VTx without any B cell-depleting pre-treatment (6 isolated intestinal transplants (IT) and 26 liver-containing, multivisceral transplants (MVT) and assessed the presence of donor-specific antibodies (DSA) pre- and posttransplantation. Twenty-one patients (65 %) developed AR, 15 (57 %) of the MVT and 6 (100 %) of the IT (p = 0.05). CR occurred in 4 IT (60 %, p < 0.001). At one month, de novo DSA were present in 71 % of VTx (66 % MVT vs 100 % IT, p = 0.09). At the last available follow-up, 69 % of the MVT and 50 % of the IT patients were DSA-free. De novo DSA seemed more persistent (7/19, 37 %) than pre-Tx DSA (1/6, 17 %; p = n.s.), de novo DSA were more frequently specific for HLA class II than class I, 16/19 (84 %) vs. 7/19 (37 %; p = 0.003), and HLA-DQ was their most frequent target HLA. DQ mismatches appeared to be a risk factor for developing de novo DSA. In conclusion, liver-containing visceral allografts have superior shortand long-term outcomes compared with liver-free allografts. De novo DSA develop early and frequently after VTx performed without B cell-depleting induction therapy, but the exact role of DSA in the pathogenesis of rejection remains unclear.
|
|
| 3. |
|
|
| 4. |
- Bergqvist, Michael, et al.
(författare)
-
Phase II randomized study of the IGF-1R pathway modulator AXL1717 compared to docetaxel in patients with previously treated, locally advanced or metastatic non-small cell lung cancer
- 2017
-
Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 53:3, s. 441-447
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The primary objective of this study was to compare the progression-free survival (PFS) at 12 weeks between patients treated with IGF-1R pathway modulator AXL1717 (AXL) and patients treated with docetaxel (DCT).MATERIAL AND METHODS: The study was conducted at 19 study centers in five countries. A total of 99 patients with previously treated, locally advanced or metastatic non-small cell lung cancer (NSCLC) of the squamous cell carcinoma (SCC) or adenocarcinoma (AC) subtypes in need of additional treatment were randomized and treated with either 300 or 400 mg of AXL as daily BID treatment (58 patients) or DCT given as 75 mg/m(2) in three-week cycles (41 patients) as monotherapy in a 3:2 ratio for each NSCLC subtype. Patients were treated in the primary study treatment period for a maximum of four treatment cycles.RESULTS: The 12-week PFS rate, median PFS and overall survival (OS), as well Kaplan-Meier hazard ratio for PFS and OS, did not show any statistically significant differences between the treatment groups. For the primary endpoint, the AXL group had a lower percentage of patients (25.9%) who were progression-free at Week 12 as compared to the DCT group (39.0%), although the difference was not statistically significant. The most notable difference in the incidence of treatment emergent adverse effects (TEAEs) was the lower incidence of treatment-related grade 3/4 neutropenia in patients treated with AXL.CONCLUSION: These results suggest neither of the treatments to be superior of the other when treating locally advanced or metastatic NSCLC. Considering the lower incidence of grade 3/4 neutropenia in the AXL group this treatment warrants further research.
|
|
| 5. |
- Brännström, Mats, 1958, et al.
(författare)
-
The first clinical uterus transplantation trial: a six-month report.
- 2014
-
Ingår i: Fertility and sterility. - : Elsevier BV. - 1556-5653 .- 0015-0282. ; 101:5, s. 1228-1236
-
Tidskriftsartikel (refereegranskat)abstract
- To report the 6-month results of the first clinical uterus transplantation (UTx) trial. This type of transplantation may become a treatment of absolute uterine-factor infertility (AUFI).
|
|
| 6. |
|
|
| 7. |
- Ceric, Ameldina, et al.
(författare)
-
Effect of level of sedation on outcomes in critically ill adult patients : a systematic review of clinical trials with meta-analysis and trial sequential analysis
- 2024
-
Ingår i: EClinicalMedicine. - 2589-5370. ; 71
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Sedation is routinely administered to critically ill patients to alleviate anxiety, discomfort, and patient-ventilator asynchrony. However, it must be balanced against risks such as delirium and prolonged intensive care stays. This study aimed to investigate the effects of different levels of sedation in critically ill adults. Methods: Systematic review with meta-analysis and trial sequential analysis (TSA) of randomised clinical trials including critically ill adults admitted to the intensive care unit. CENTRAL, MEDLINE, Embase, LILACS, and Web of Science were searched from their inception to 13 June 2023. Risks of bias were assessed using the Cochrane risk of bias tool. Primary outcome was all-cause mortality. Aggregate data were synthesised with meta-analyses and TSA, and the certainty of the evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. This study is registered with PROSPERO: CRD42023386960. Findings: Fifteen trials randomising 4352 patients were included, of which 13 were assessed high risk of bias. Meta-analyses comparing lighter to deeper sedation showed no evidence of a difference in all-cause mortality (risk ratio (RR) 0.94, 95% confidence interval (CI) 0.83–1.06; p = 0.28; 15 trials; moderate certainty evidence), serious adverse events (RR 0.99, CI 0.92–1.06; p = 0.80; 15 trials; moderate certainty evidence), or delirium (RR 1.01, 95% CI 0.94–1.09; p = 0.78; 11 trials; moderate certainty evidence). TSA showed that when assessing mortality, a relative risk reduction of 16% or more between the compared interventions could be rejected. Interpretation: The level of sedation has not been shown to affect the risks of death, delirium, and other serious adverse events in critically ill adult patients. While TSA suggests that additional trials are unlikely to significantly change the conclusion of the meta-analyses, the certainty of evidence was moderate. This suggests a need for future high-quality studies with higher methodological rigor. Funding: None.
|
|
| 8. |
- Ceric, Ameldina, et al.
(författare)
-
Level of sedation in critically ill adult patients : a protocol for a systematic review with meta-analysis and trial sequential analysis
- 2022
-
Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 12:9
-
Forskningsöversikt (refereegranskat)abstract
- Introduction It is standard of care to provide sedation to critically ill patients to reduce anxiety, discomfort and promote tolerance of mechanical ventilation. Given that sedatives can have differing effects based on a variety of patient and pharmacological characteristics, treatment approaches are largely based on targeting the level of sedation. The benefits of differing levels of sedation must be balanced against potential adverse effects including haemodynamic instability, causing delirium, delaying awakening and prolonging the time of mechanical ventilation and intensive care stay. This systematic review with meta-analysis aims to investigate the current evidence and compare the effects of differing sedation levels in adult critically ill patients. Methods and analyses We will conduct a systematic review based on searches of preidentified major medical databases (eg, MEDLINE, EMBASE, CENTRAL) and clinical trial registries from their inception onwards to identify trials meeting inclusion criteria. We will include randomised clinical trials comparing any degree of sedation with no sedation and lighter sedation with deeper sedation for critically ill patients admitted to the intensive care unit. We will include aggregate data meta-analyses and trial sequential analyses. Risk of bias will be assessed with domains based on the Cochrane risk of bias tool. An eight-step procedure will be used to assess if the thresholds for clinical significance are crossed, and the certainty of the evidence will be assessed using Grades of Recommendations, Assessment, Development and Evaluation. Ethics and dissemination No formal approval or review of ethics is required as individual patient data will not be included. This systematic review has the potential to highlight (1) whether one should believe sedation to be beneficial, harmful or neither in critically ill adults; (2) the existing knowledge gaps and (3) whether the recommendations from guidelines and daily clinical practice are supported by current evidence. These results will be disseminated through publication in a peer-reviewed journal.
|
|
| 9. |
- Danared, Håkan, et al.
(författare)
-
Preface
- 2017
-
Ingår i: IPAC 2018 : Proceedings of the 8th International Particle Accelerator Conference - Proceedings of the 8th International Particle Accelerator Conference. - 9783954501823
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
| 10. |
|
|
